The FDA launched a structured effort to pressure-test how it handles statistical trade-offs in rare-disease programs. Ahead of a Sept. 29 RISE workshop, the agency is seeking public input on the statistical considerations that influence endpoint selection and efficacy determinations for both drugs and devices in rare diseases. The move comes as regulators face growing scrutiny over how to balance feasibility—often limited patient populations—with the need for sufficiently informative evidence. For developers, the workshop agenda signals that the FDA wants more clarity on how it will interpret efficacy when trial designs depart from traditional large-population settings. The outcome could influence future development plans for rare-disease candidates now navigating accelerated timelines and bespoke endpoints, particularly where confirmatory evidence is difficult to generate.